Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies revealed that administration of 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] to calcium (Ca)-deficient rats causes a dose-dependent reduction in markedly elevated serum 1,25-(OH)2D3 level. Although the results suggested that the metabolism of 1,25-(OH)2D3 was accelerated by 24,25-(OH)2D3, those experiments could not define whether the enhanced metabolism of 1,25-(OH)2D3 played a role in the reduction in the serum 1,25-(OH)2D3 level. In the present study, in order to address this issue more specifically, serum 1,25-(OH)2D3 was maintained solely by exogenous administration through miniosmotic pumps of 1,25-(OH)2D3 into vitamin D-deficient rats. Thus, by measuring the serum 1,25-(OH)2D3 concentration, the effect of 24,25-(OH)2D3 on the MCR of 1,25-(OH)2D3 could be examined. Administration of 24,25-(OH)2D3 caused a dose-dependent enhancement in the MCR of 1,25-(OH)2D3, and 1 microgram/100 g rat.day 24,25-(OH)2D3, which elevated serum 24,25-(OH)2D3 to 8.6 +/- 1.3 ng/ml, significantly increased MCR and suppressed serum levels of 1,25-(OH)2D3. The effect of 24,25-(OH)2D3 on 1,25-(OH)2D3 metabolism developed with a rapid time course, and the recovery of iv injected [1 beta-3H]1,25-(OH)2D3 in blood was significantly reduced within 1 h. In addition, there was an increase in radioactivity in the water-soluble fraction of serum as well as in urine, suggesting that 1,25-(OH)2D3 is rapidly degraded to a water-soluble metabolite(s). Furthermore, the reduction in serum 1,25-(OH)2D3 was associated with a reduction in both serum and urinary Ca levels. Because the conversion of [3H]24,25-(OH)2D3 to [3H]1,24,25-(OH)2D3 or other metabolites was minimal in these rats, 24,25-(OH)2D3 appears to act without being converted into other metabolites. These results demonstrate that 24,25-(OH)2D3 rapidly stimulates the metabolism of 1,25-(OH)2D3 and reduces its serum level. It is suggested that 24,25-(OH)2D3 plays a role in modifying serum 1,25-(OH)2D3 concentrations by affecting the metabolism of 1,25-(OH)2D3 and may have a therapeutic values in the treatment of hypercalcemia or hypercalciuria caused by 1,25-(OH)2D3 excess.
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PMID:Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] metabolism in vitamin D-deficient rats infused with 1,25-(OH)2D3. 278 9

Previous studies of 1,25-dihydroxyvitamin D [1,25-(OH)2D] kinetics in normal subjects using the pulse injection technique have led to conflicting results, and only limited data are available concerning 1,25-(OH)2D kinetics in hypercalciuric patients. We developed an infusion equilibrium technique that measures the metabolic clearance and production rates of 1,25-(OH)2D and applied this technique in 13 normal subjects and 9 well characterized patients with absorptive hypercalciuria; all subjects were studied after 10 days on a 400-mg calcium intake. All subjects received a constant infusion of [3H]1,25-(OH)2D3 (20,000 dpm/min). Purified plasma radioactivity reached steady state levels after 15 h, and between 15 and 19 h, serial measurements of purified plasma radioactivity and endogenous 1,25-(OH)2D were made for calculation of metabolic clearance and production rates. In the 13 normal subjects, the MCR values were within a narrow range, with a mean +/- SD value of 37 +/- 6 ml/min, which, when combined with the mean steady state concentration of endogenous 1,25-(OH)2D (42 +/- 6 pg/ml), yielded a mean production rate of 2.2 +/- 0.5 micrograms/day. In the 9 patients with absorptive hypercalciuria, MCR values also were tightly clustered, with a mean of 35 +/- 4 ml/min. However, the mean endogenous steady state 1,25-(OH)2D level was significantly elevated in these patients, such that the calculated mean 1,25-(OH)2D production rate was significantly elevated at 3.4 +/- 0.5 micrograms/day. In 7 of the 9 patients with absorptive hypercalciuria, production rates exceeded the highest values found in the normal subjects. These data demonstrate disordered 1,25-(OH)2D production as opposed to metabolic clearance in the syndrome of absorptive hypercalciuria.
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PMID:Elevated production rate of 1,25-dihydroxyvitamin D in patients with absorptive hypercalciuria. 299 23

We determined the metabolic clearance and production rates of 1,25-dihydroxyvitamin D [1,25-(OH)2D] in 5 patients with sarcoidosis who had either hypercalciuria or hypercalcemia to examine whether abnormalities in the metabolism of this hormone existed. The mean MCR in the 5 patients with sarcoidosis [40 +/- 9 (+/- SD) mL/min] was similar to that in 13 normal subjects (37 +/- 6 mL/min) and that in 9 patients with absorptive hypercalciuria and renal stones (35 +/- 4 mL/min). However, the mean serum 1,25-(OH)2D concentration was significantly higher in the patients with sarcoidosis (211 +/- 60 pmol/L) than in either of the other 2 groups. The mean 1,25-(OH)2D production rate was markedly elevated in the patients with sarcoidosis (12.4 +/- 5.3 mumol/day), being more than 2-fold greater than the normal mean value (5.4 +/- 1.2 mumol/day). The highest production rates were found in patients with hypercalcemia, whereas subjects with hypercalciuria had production rates comparable to those in the patients with absorptive hypercalciuria. These data indicate that there is no impairment in the clearance of 1,25-(OH)2D in patients with sarcoidosis and that the elevated serum 1,25-(OH)2D levels are due to an increase in its production rate.
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PMID:Enhanced production rate of 1,25-dihydroxyvitamin D in sarcoidosis. 333 11